Epirubicin, cisplatin plus ifosfamide versus standard chemotherapeutic regimens for advanced/unresectable primary thoracic sarcomas

J Cancer Res Clin Oncol. 2023 Aug;149(9):5479-5491. doi: 10.1007/s00432-022-04454-8. Epub 2022 Dec 4.

Abstract

Purpose: Thoracic sarcomas are rare malignancies, with limited data for unresectable/advanced scenarios. Our goal is to provide insights of a three-drug chemotherapy regimen improving patient survival compared to standard regimens.

Methods: Retrospective cohort analysis of patients diagnosed with unresectable/advanced primary thoracic sarcoma divided between primary pulmonary sarcomas (PPS) and chest wall sarcomas (CWS) comparing chemotherapeutical regimens efficacy. Not true soft tissue sarcomas (STS) for PPS were excluded from the analysis. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier with hazard ratio (HR) obtained via Mantel-Haenszel or log rank.

Results: 157 total cases were included, from which 50 cases were PPS and 107 cases CWS. For PPS, 4 cases were excluded from the analysis as they were not true STS. The most common histology was undifferentiated sarcomas, 63% of cases were treated with E/C/I and 37% with another regimen. The E/C/I regimen demonstrated a benefit for both OS (p = 0.020) and PFS (p = 0.010) when compared to any other regimen as well as when compared to non-platinum regimens (p = 0.016 and p = 0.001). Regarding CWS, the most common histology was synovial and undifferentiated sarcomas, 55.1% were treated with E/C/I and 44.9% treated with another regimen. The E/C/I regimen did not demonstrate a benefit for OS or PFS compared to any other regimen, neither when compared to other non-platinum regimens. However, a benefit was observed in favor of E/C/I when compared to other platinum regimens in both OS (p = 0.049) and PFS (0.015). Both analyses for PPS and CWS demonstrated a benefit in favor of cisplatin therapies compared to carboplatin in both OS and PFS.

Conclusion: This study demonstrates that platinum therapy alone does not work, and that cisplatin must be the agent of choice and it's used in combination could increase treatment response. The E/C/I regimen demonstrated a in PPS but not for CWS, this is due do their rarity of PPS and that no standard treatment is established yet. The regimen proposed here could represent a possible new standard of treatment for PPS as long as it is validated in a prospective study.

Keywords: Antineoplastic combined chemotherapy; Chest wall sarcomas; Cisplatin; Epirubicin; Ifosfamide; Primary pulmonary sarcomas; Survival analysis.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cisplatin
  • Epirubicin
  • Humans
  • Ifosfamide
  • Prospective Studies
  • Retrospective Studies
  • Sarcoma* / pathology
  • Soft Tissue Neoplasms*

Substances

  • Cisplatin
  • Ifosfamide
  • Epirubicin